Search

Ankylosing spondylitis (AS) is a chronic inflammatory disorder primarily affecting the sacroiliac joints and the spine. T-cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) has been established as a negative regulatory molecule that plays a critical role in controlling inflammation. Studies have shown that polymorphisms in TIM-3 gene may be associated with inflammatory diseases. The current study investigated the association between polymorphisms in the TIM-3 gene and susceptibility to AS, and it examined the effects of these polymorphisms on gene expression. Two polymorphisms in TIM-3 −574G/T and +4259T/G polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism in 282 AS patients and 298 healthy controls. Results showed that frequency of the TIM-3 −574GT genotype was significantly increased in cases than in controls (Odd ratio [OR]=2.50, 95% confidence interval [CI]: 1.39-4.48, p=0.002). Similarly, TIM-3 −574T allele revealed a positive association with the disease (OR=2.39, p=0.002). The TIM-3 +4259T/G polymorphism did not show any correlation with AS. We further evaluated TIM-3 mRNA and protein levels in CD4+ T cells, CD8+ T cells, and monocytes from subjects carrying different TIM-3 genotypes. Results revealed that subjects carrying polymorphic −574GT genotype had significantly lower TIM-3 mRNA and protein levels in CD4+ T cells, CD8+ T cells, and monocytes than those with wild-type GG genotype. These data suggest that TIM-3 polymorphism is associated with increased susceptibility to AS possibly by downregulating gene expression. [ABSTRACT FROM AUTHOR]

The activation of a hemostatic system plays a critical role in the incidence of acute coronary events. Hemostatic proteins may be regulated by microRNAs (miRNAs). Microparticles (MPs) are the major carrier of circulating miRNAs. The aim of this study was to determine the potential role of miRNAs in regulating gene expression involved in the hemostatic system in patients with unstable angina (UA). MiRNA expression profiles in the plasma from patients with UA (UA group, n = 9) compared with individuals with clinical suspicion of coronary artery disease (CAD) but negative angiography (control group, n = 9) showed that among 36 differentially expressed miRNAs, miR-19b was the most obvious one. Using real-time PCR, 5 selected miRNA levels in plasma (UA group, n = 20; control group, n = 30) and plasma MPs (UA group n = 6; control group n = 6) were proved to be consistent with the miRNA array. Flow cytometry analysis indicated that the amounts of plasma endothelial microparticles (EMPs) were increased in UA patients (UA group, n = 4) compared to controls (control group, n = 4). In cultured endothelial cells (ECs), TNF-α increased miR-19b release and expression. Tissue factor (TF) was predicted to be the target of miR-19b by bioinformatics analysis. Luciferase reporter assays demonstrated that miR-19b binds to TF mRNA. Overexpression of miR-19b inhibited TF expression and procoagulant activity. This study indicates that in UA patients, the increase of miR-19b wrapped in EMPs due to endothelial dysfunction may partially contribute to the circulating miR-19b elevation and miR-19b may play an anti-thrombotic role by inhibiting the expression of TF in ECs. [ABSTRACT FROM AUTHOR]